Kaikita Koichi, Ishii Masanobu, Sato Koji, Nakayama Masafumi, Arima Yuichiro, Tanaka Tomoko, Sugamura Koichi, Sakamoto Kenji, Izumiya Yasuhiro, Yamamoto Eiichiro, Tsujita Kenichi, Yamamuro Megumi, Kojima Sunao, Soejima Hirofumi, Hokimoto Seiji, Matsui Kunihiko, Ogawa Hisao
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan (K.K., M.I., K.S., M.N., Y.A., T.T., K.S., K.S., Y.I., E.Y., K.T., M.Y., S.K., H.S., S.H., H.O.).
Department of Community Medicine, Kumamoto University Hospital, Kumamoto, Japan (K.M.).
J Am Heart Assoc. 2015 Dec 11;4(12):e002387. doi: 10.1161/JAHA.115.002387.
Myocardial lactate production in the coronary circulation during acetylcholine (ACh)-provocation test (abbreviated as lactate production) provides supporting evidence for coronary spasm-induced myocardial ischemia. The purpose of this study was to examine the clinical features, predictive factors, and prognosis of patients with coronary vasospastic angina (VSA) and lactate production.
We examined all 712 patients who underwent both myocardial lactate measurement during ACh-provocation test in the left coronary artery and genetic screening test of a -786T/C polymorphism in the 5'-flanking region of the endothelial nitric oxide synthase (eNOS) gene between January 1991 and December 2010. Lactate production was observed in 252 of the 712 patients and in 219 of 356 VSA patients diagnosed by ACh-provocation test. Compared with lactate production-negative VSA patients, the lactate production-positive counterparts were more likely to be nonsmoker female diabetics with -786T/C eNOS polymorphism (61% vs 31%, P<0.001, 62% vs 34%, P<0.001, 24% vs 14%, P=0.016, and 25% vs 15%, P=0.018, respectively). Multivariable logistic regression analysis identified female sex, diabetes mellitus, and -786T/C eNOS polymorphism to correlate with lactate production (odds ratio 3.51, 95% CI 2.16 to 5.70, P<0.001; odds ratio 2.53, 95% CI 1.38 to 4.65, P=0.003; and odds ratio 1.85, 95% CI 1.02 to 3.35, P=0.044, respectively). Kaplan-Meier survival curve showed no difference in 5-year survival rate free from major adverse cardiac events between lactate production-positive and -negative VSA patients (P=0.319).
The results indicated that female sex, diabetes, and mutation in -786T/C eNOS gene correlate with ACh-provoked myocardial ischemia in patients with coronary spasm.
乙酰胆碱（ACh）激发试验期间冠状动脉循环中的心肌乳酸生成（简称为乳酸生成）为冠状动脉痉挛诱发的心肌缺血提供了支持性证据。本研究的目的是探讨冠状动脉痉挛性心绞痛（VSA）伴乳酸生成患者的临床特征、预测因素和预后。
我们对1991年1月至2010年12月期间接受左冠状动脉ACh激发试验心肌乳酸测量以及内皮型一氧化氮合酶（eNOS）基因5'侧翼区-786T/C多态性基因筛查试验的所有712例患者进行了检查。712例患者中有252例出现乳酸生成，在通过ACh激发试验诊断的356例VSA患者中有219例出现乳酸生成。与乳酸生成阴性的VSA患者相比，乳酸生成阳性的患者更可能是患有-786T/C eNOS多态性的非吸烟女性糖尿病患者（分别为61%对31%，P<0.001；62%对34%，P<0.001；24%对14%，P=0.016；25%对15%，P=0.018）。多变量逻辑回归分析确定女性、糖尿病和-786T/C eNOS多态性与乳酸生成相关（比值比分别为3.51，95%可信区间2.16至5.70，P<0.001；比值比2.53，95%可信区间1.38至4.65，P=0.003；比值比1.85，95%可信区间1.02至3.35，P=0.044）。Kaplan-Meier生存曲线显示，乳酸生成阳性和阴性的VSA患者在5年无主要不良心脏事件生存率方面无差异（P=0.319）。
结果表明，女性、糖尿病和-786T/C eNOS基因突变与冠状动脉痉挛患者ACh诱发的心肌缺血相关。
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